Survival has improved but neurobehavioral disabilty remains a common complication with adverse impacts on quality of life, educational and occupational attainments, and resource utilization. There is increasing evidence that brain development is abnormal, and leads to a rrisk of peri-operative brain injury.
Studies are needed to;
1. Further define the prevalence and spectrum of neurobehavioral disability.
2, Understand
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Survival has improved following surgery for complex congenital heart disease. There is an ever increasing population of adolescents and adults with repaired congenital heart defects. Neurobehvaioral disability can be identified in over 50% of survivors, including ADHD, autism spectrum disorders, learning disabilities and impaired motor skills. These deficits adversly affect their schools and job performance, as well as interactions with their peers and families. The need for special education and other rehabilitative services leads to significant resurce utilization and costs to society. Development of novel neuroprotective therapies will significantly improve the long-term outcomes for these fragile children.

Feasibility and challenges of addressing this CQ or CC:

Because of the small numbers of patients treated at single instituions, this project will require multi-institutional collaboration with long-term follow-up assessments. There is need for collabortaive databases, standardized neurodevelopment evaluations, and acquistion of genomic data. In particular, there is a need to development methodolgy to track outcomes from fetal life to adulthood.

Name of idea submitter and other team members who worked on this idea:
J William Gaynor

Voting

What is the effect of sleep disorders on child development? Specifically, how sleep apnea with intermittent hypoxia and or sleep deprivation alters the normal trajectory of maturation of brain regions controlling cognition, behavior and the cardiovascular system?

The significance of the behavioral and cardiovascular findings in children as they relate to health during adulthood is unknown. It remains to be defined whether the behavioral and cardiovascular abnormalities observed in children with sleep apnea are a reflection of structural and functional brain abnormalities, which might persist into adulthood and predispose to health problems at an older age.

A fundamental question that deserve investigation whether brain maturation in children with sleep apnea and sleep deprivation deviate from normal trajectory and whether brain plasticity can restore normal structure and function.

Such knowledge on brain maturation and plasticity in children with sleep disorders could lead to the identification of brain biomarkers that might signal risk for future mood and behavioral disorders and or cardiovascular diseases. The new knowledge will also identify sensitive period(s) during child development for interventions.

Feasibility and challenges of addressing this CQ or CC:

In the last decade, the application of new technologies of fMRI and diffusion MRI have permitted the study of the evolving brain connectome across all stages of development and created new potentials to inform our etiologic understanding of many pediatric and adult diseases.

We now can for the first time examine the brain developmental trajectories in children with chronic medical conditions including sleep disorders and compare the findings to normative data.

Name of idea submitter and other team members who worked on this idea:
Raouf Amin, Mark DiFrancesco, Scott Holland

Voting

The analysis of lipoprotein metabolism has traditionally been restricted to the easily accessible circulation and peripheral tissues. Very little work has been done behind the blood brain barrier, where many of the lipid carrying or metabolizing genes are also expressed. Yet we know very little about their functions there, although for instance ApoE4 is THE primary risk factor for late-onset Alzheimer's disease. Conventional
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Alzheimer's disease currently affects ~6 million Americans and costs upwards of 200 billion $ per year. Lipoprotein components, specifically containing ApoE and ApoJ, are the predominant risk factors for late-onset AD. The neuroscience community lacks the expertise in lipoprotein biology that is necessary to solve this enormous socioeconomic problem.

The NHLBI is ideally positioned to assume a leadership role to address this major challenge, which transcends traditional institute boundaries.

Feasibility and challenges of addressing this CQ or CC:

This is perfectly feasible, I am addressing this problem for years, there are clear rational approaches for it, but far too few investigators have picked up the challenge.

I would be most interested in discussing strategies and solutions to this pressing challenge in detail with the NHLBI!

Name of idea submitter and other team members who worked on this idea:
Joachim Herz

Voting

Cerbrospinal fluid flow and waste clearance through glyphatic pathways are likely to be important in numerous brain diseases including such devastating diseases such as alzheimer's , parkinson's, stroke and migraine. However, relatively little is known about the brain's waste clearance mechanisms, and how failure in these systems may underlie brain disease. Build up of proteins and calcification have been shown to
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Studies on the etiology of migraine, stroke, motor disturbance, hydrocephalus, mental health and alzheimer's and numerous other brain diseases have overlooked the possible dysfuncton of brain waste clearance mechanisms. Similar to the case for renal failure, build up of toxic wastes in the brain may impact all aspects of brain health. A dedicated effort in understanding how the brain clears waste and the conditions that cause this to be imparied may open completely new avenues for treatment of debiltating brain diseases.

Feasibility and challenges of addressing this CQ or CC:

Very little is known about the choroid plexus and other CSF generating tissues, the regulation of CSF compostioin and its flow through newly discovered glymphatic pathways. Furthermore, the challenge is determining whether deficiencies of these processes affect brain health. New technologies allow us to visualize the brain and CSF as never below, and can help us to make these connections. Furthermore, our advancing understanding of brain anatomy makes further investigation in this area timely and feasible.

Name of idea submitter and other team members who worked on this idea:
Ceci Giachelli

Voting

Dangerous mechanical interaction of the cerebral vascular system with the brain parenchyma during mild traumatic brain injury from either a blast wave or from impact may result from a combination of shear and compression deformation waves that causes non-diffusive extracellular fluid motion. Measure the mechanical response, to a combination of shear and compressive deformation, of animal model specimens containing the
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Such research would give insight into the immediate mechanical causes of cerebral artery dissection or of mild traumatic brain injury that occur prior to observed biochemical responses and would lay a foundation for counter-measures.

Feasibility and challenges of addressing this CQ or CC:

Develop a mathematical model for the mechanical interaction of the vascular system with the brain parenchyma and for flow in the glymphatic system during mild traumatic brain injury to predict forces generated in the extracellular fluid and in the walls of the cerebral arteries.

Name of idea submitter and other team members who worked on this idea:
Henry W. Haslach, Jr.

To extend our knowledge of the pathobiology of heart, lung, blood, and sleep disorders and enable clinical investigations that advance the prediction, prevention, preemption, treatment, and cures of human disease.